The goal of this program is to define new strategies and methods for the synthesis of bioactive molecules. The small molecules that we construct can provide tools to study biological processes and may ultimately be used to develop new therapeutics. These studies will also lead to a better understanding of organic functional group reactivity. Specifically, we intend to develop a general strategy for the synthesis of the sesterterpene compounds neomangicol C and mangicol A. These compounds possess antitumor, antibacterial and anti-inflammatory properties. We also present a novel iodine-mediated pentannulation reaction that will be applied to the synthesis of a series of resveratrol-derived natural products. It is our anticipation that these new methodological developments for pentannulation will streamline the synthesis of complex molecules. The total synthesis of the natural products drives the development of new methods and strategies. In turn, these new developments will be applied to the synthesis of other molecules of biological and structural interest. These contributions will aid advances in human medicine and chemical biology by providing a synthesis foundation. PUBLIC HEALTH RELEVANCE: Finding new and more efficient ways to construct small molecules is an important pursuit that will provide new tools for chemical biology and medicine and lead to improvements in human health. Our goals are to develop new strategies and methods that efficiently build small molecules that are of pharmaceutical importance and natural products. In this regard, we are especially interested in new five-membered ring forming reactions using transition metals.